Publications & Presentations


1. InterLACE: A new International Collaboration for a Life Course Approach to Women’s Reproductive Health and Chronic Disease Events

Mishra GD, Anderson D, Schoenaker DAJM, Adami HO, Avis NE, Brown D, . . . , Weiderpass E. InterLACE: A new International Collaboration for a Life Course Approach to Women's Reproductive Health and Chronic Disease Events. Maturitas. 2013;74(3):235-40.

Abstract: Evidence from population-based studies of women increasingly points to the inter-related nature of reproductive health, lifestyle, and chronic disease risk. This paper describes the recently established International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease. InterLACE aims to advance the evidence base for women's health policy beyond associations from disparate studies by means of systematic and culturally sensitive synthesis of longitudinal data. Currently InterLACE draws on individual level data for reproductive health and chronic disease among 200,000 women from over thirteen studies of women's health in seven countries. The rationale for this multi-study research programme is set out in terms of a life course perspective to reproductive health. The research programme will build a comprehensive picture of reproductive health through life in relation to chronic disease risk. Although combining multiple international studies poses methodological challenges, InterLACE represents an invaluable opportunity to strength evidence to guide the development of timely and tailored preventive health strategies.

2. The InterLACE study: Design, data harmonization and characteristics across 20 studies on women's health

Mishra GD, Chung HF, Pandeya N, Dobson AJ, Jones L, Avis NE, . . . , Anderson D. The InterLACE study: Design, data harmonization and characteristics across 20 studies on women's health. Maturitas. 2016;92:176-85.

OBJECTIVES: The International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE) project is a global research collaboration that aims to advance understanding of women's reproductive health in relation to chronic disease risk by pooling individual participant data from several cohort and cross-sectional studies. The aim of this paper is to describe the characteristics of contributing studies and to present the distribution of demographic and reproductive factors and chronic disease outcomes in InterLACE.
STUDY DESIGN: InterLACE is an individual-level pooled study of 20 observational studies (12 of which are longitudinal) from ten countries. Variables were harmonized across studies to create a new and systematic synthesis of life-course data.
MAIN OUTCOME MEASURES: Harmonized data were derived in three domains: 1) socio-demographic and lifestyle factors, 2) female reproductive characteristics, and 3) chronic disease outcomes (cardiovascular disease (CVD) and diabetes).
RESULTS: InterLACE pooled data from 229,054 mid-aged women. Overall, 76% of the women were Caucasian and 22% Japanese; other ethnicities (of 300 or more participants) included Hispanic/Latin American (0.2%), Chinese (0.2%), Middle Eastern (0.3%), African/black (0.5%), and Other (1.0%). The median age at baseline was 47 years (Inter-quartile range (IQR): 41-53), and that at the last follow-up was 56 years (IQR: 48-64). Regarding reproductive characteristics, half of the women (49.8%) had their first menstruation (menarche) at 12-13 years of age. The distribution of menopausal status and the prevalence of chronic disease varied considerably among studies. At baseline, most women (57%) were pre- or peri-menopausal, 20% reported a natural menopause (range 0.8-55.6%) and the remainder had surgery or were taking hormones. By the end of follow-up, the prevalence rates of CVD and diabetes were 7.2% (range 0.9-24.6%) and 5.1% (range 1.3-13.2%), respectively.
CONCLUSIONS: The scale and heterogeneity of InterLACE data provide an opportunity to strengthen evidence concerning the relationships between reproductive health through life and subsequent risks of chronic disease, including cross-cultural comparisons.

3. Early menarche, nulliparity and the risk for premature and early natural menopause

Mishra GD, Pandeya N, Dobson AJ, Chung HF, Anderson D, Kuh D, . . . , Weiderpass E. Early menarche, nulliparity and the risk for premature and early natural menopause. Human Reproduction. 2017; doi: 10.1093/humrep/dew350 [Epub ahead of print].

STUDY QUESTION: Are parity and the timing of menarche associated with premature and early natural menopause?
SUMMARY ANSWER: Early menarche (≤11 years) is a risk factor for both premature menopause (final menstrual period, FMP <40 years) and early menopause (FMP 40-44 years), a risk that is amplified for nulliparous women.
WHAT IS KNOWN ALREADY: Women with either premature or early menopause face an increased risk of chronic conditions in later life and of early death. Findings from some studies suggest that early menarche and nulliparity are associated with early menopause, however overall the evidence is mixed. Much of the evidence for a direct relationship is hampered by a lack of comparability across studies, failure to adjust for confounding factors and inadequate statistical power.
STUDY DESIGN, SIZE, DURATION: This pooled study comprises 51 450 postmenopausal women from nine observational studies in the UK, Scandinavia, Australia and Japan that contribute to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE).
PARTICIPANTS/MATERIALS, SETTING, METHODS: Age at menarche (categorized as ≤11, 12, 13, 14 and 15 or more years) and parity (categorized as no children, one child and two or more children) were exposures of interest. Age at FMP was confirmed by at least 12 months of cessation of menses where this was not the result of an intervention (such as surgical menopause due to bilateral oophorectomy or hysterectomy) and categorized as premature menopause (FMP before age 40), early menopause (FMP 40-44 years), 45-49 years, 50-51 years, 52-53 years and 54 or more years. We used multivariate multinomial logistic regression models to estimate relative risk ratio (RRR) and 95% CI for associations between menarche, parity and age at FMP adjusting for within-study correlation.
MAIN RESULTS AND THE ROLE OF CHANCE: The median age at FMP was 50 years (interquartile range 48-53 years), with 2% of the women experiencing premature menopause and 7.6% early menopause. Women with early menarche (≤11 years, compared with 12-13 years) were at higher risk of premature menopause (RRR 1.80, 95% CI 1.53-2.12) and early menopause (1.31, 1.19-1.44). Nulliparity was associated with increased risk of premature menopause (2.26, 1.84-2.77) and early menopause (1.32, 1.09-1.59). Women having early menarche and nulliparity were at over 5-fold increased risk of premature menopause (5.64, 4.04-7.87) and 2-fold increased risk of early menopause (2.16, 1.48-3.15) compared with women who had menarche at ≥12 years and two or more children.
LIMITATIONS, REASONS FOR CAUTION: Most of the studies (except the birth cohorts) relied on retrospectively reported age at menarche, which may have led to some degree of recall bias.
WIDER IMPLICATIONS OF THE FINDINGS: Our findings support early monitoring of women with early menarche, especially those who have no children, for preventive health interventions aimed at mitigating the risk of adverse health outcomes associated with early menopause.
STUDY FUNDING/COMPETING INTERESTS: InterLACE project is funded by the Australian National Health and Medical Research Council project grant (APP1027196). G.D.M. is supported by Australian Research Council Future Fellowship (FT120100812). There are no competing interests.

Related publications: 

1. Menopause

Davis SR, Lambrinoudaki I, Lumsden M, Mishra GD, Pal L, Rees M, Santoro N, Simoncini T. Menopause. Nature Reviews Disease Primers. 15004 (2015) doi:10.1038/nrdp.2015.4

Abstract: Menopause is an inevitable component of ageing and encompasses the loss of ovarian reproductive function, either occurring spontaneously or secondary to other conditions. It is not yet possible to accurately predict the onset of menopause, especially early menopause, to give women improved control of their fertility. The decline in ovarian oestrogen production at menopause can cause physical symptoms that may be debilitating, including hot flushes and night sweats, urogenital atrophy, sexual dysfunction, mood changes, bone loss, and metabolic changes that predispose to cardiovascular disease and diabetes. The individual experience of the menopause transition varies widely. Important influential factors include the age at which menopause occurs, personal health and wellbeing, and each woman's environment and culture. Management options range from lifestyle assessment and intervention through to hormonal and non-hormonal pharmacotherapy, each of which has specific benefits and risks. Decisions about therapy for perimenopausal and postmenopausal women depend on symptomatology, health status, immediate and long-term health risks, personal life expectations, and the availability and cost of therapies. More effective and safe therapies for the management of menopausal symptoms need to be developed, particularly for women who have absolute contraindications to hormone therapy.

2. Socioeconomic position, lifestyle factors and age at natural menopause: a systematic review and meta-analyses of studies across six continents

Schoenaker DAJM, Jackson CA, Rowlands JV, Mishra GD. Socioeconomic position, lifestyle factors and age at natural menopause: a systematic review and meta-analyses of studies across six continents. International Journal of Epidemiology. 2014;43(5):1542-62.

BACKGROUND: Age at natural menopause (ANM) is considered a marker of biological ageing and is increasingly recognized as a sentinel for chronic disease risk in later life. Socioeconomic position (SEP) and lifestyle factors are thought to be associated with ANM.
METHODS: We performed a systematic review and meta-analyses to determine the overall mean ANM, and the effect of SEP and lifestyle factors on ANM by calculating the weighted mean difference (WMD) and pooling adjusted hazard ratios. We explored heterogeneity using meta-regression and also included unpublished findings from the Australian Longitudinal Study on Women's Health.
RESULTS: We identified 46 studies across 24 countries. Mean ANM was 48.8 years [95% confidence interval (CI): 48.3, 49.2], with between-study heterogeneity partly explained by geographical region. ANM was lowest among African, Latin American, Asian and Middle Eastern countries and highest in Europe and Australia, followed by the USA. Education was associated with later ANM (WMD middle vs low education 0.30, 95% CI: 0.10, 0.51; high vs low education 0.64, 95% CI 0.26, 1.02). A similar dose-response relationship was also observed for occupation. Smoking was associated with a 1-year reduction of ANM (WMD: -0.91, 95% CI: -1.34, -0.48). Being overweight and moderate/high physical activity were modestly associated with later ANM, but findings were less conclusive.
CONCLUSIONS: ANM varies across populations, partly due to differences across geographical regions. SEP and some lifestyle factors are associated with ANM, but further research is needed to examine the impact of the associations between risk factors and ANM on future health outcomes.

3. Age at menarche, level of education, parity and the risk of hysterectomy: a systematic review and meta-analyses of population-based observational studies

Wilson LF, Mishra GD. Age at menarche, level of education, parity and the risk of hysterectomy: a Systematic review and meta-analyses of population-based observational studies. PLoS One. 2016:11(3):e0151398.

BACKGROUND: Although rates have declined, hysterectomy is still a frequent gynaecological procedure. To date, there has been no systematic quantification of the relationships between early/mid-life exposures and hysterectomy. We performed a systematic review and meta-analyses to quantify the associations between age at menarche, education level, parity and hysterectomy.
METHODS: Eligible studies were identified by searches in PubMed and Embase through March 2015. Study-specific estimates were summarised using random effects meta-analysis. Heterogeneity was explored using sub-group analysis and meta-regression.
RESULTS: Thirty-two study populations were identified for inclusion in at least one meta-analysis. Each year older at menarche was associated with lower risk of hysterectomy-summary hazard ratio 0.86 (95% confidence interval: 0.78, 0.95; I2 = 0%); summary odds ratio 0.88 (95% confidence interval: 0.82, 0.94; I2 = 61%). Low education levels conferred a higher risk of hysterectomy in the lowest versus highest level meta-analysis (summary hazard ratio 1.87 (95% confidence interval: 1.25, 2.80; I2 = 86%), summary odds ratio 1.51 (95% confidence interval: 1.35, 1.69; I2 = 90%)) and dose-response meta-analysis (summary odds ratio 1.17 (95% confidence interval: 1.12, 1.23; I2 = 85%) per each level lower of education). Sub-group analysis showed that the birth cohort category of study participants, the reference category used for level of education, the year the included article was published, quality of the study (as assessed by the authors) and control for the key variables accounted for the high heterogeneity between studies in the education level meta-analyses. In the meta-analyses of studies of parity and hysterectomy the results were not statistically significant.
CONCLUSIONS: The present meta-analyses suggest that the early life factors of age at menarche and lower education level are associated with hysterectomy, although this evidence should be interpreted with some caution due to variance across the included studies.

Invited presentations:

1. What have we learned from longitudinal studies of women’s health?

Mishra GD. The 15th World Congress on menopause, 29th of September 2016, Prague, Czech Republic.

2. What do leading women’s studies tell us about equality and empowerment to address gender based violence? Findings from ALSWH and InterLACE

Mishra GD. Co-host side event with Australian Federal Government at the 60th UN Commission on the Status of Women (CSW60), 14-24th of March 2016, New York, USA.

3. Future directions to ensure health & mental health for girls and women

Mishra GD. The 59th UN Commission on the Status of Women (CSW59), 17th of March 2015, New York, USA.

4. Reproductive health across the life course and chronic disease events: results from over 230 000 women across 10 countries

Mishra GD. RCOG/RANZCOG World Congress, 14th of April 2015, Brisbane, Australia.

5. InterLACE: A new international collaboration for a life course approach to women's reproductive health and chronic disease events

Mishra GD. ICOWHI 19th International Congress on Women's Health, 14-16th of November 2012, Bangkok, Thailand.

Mishra GD. The 3rd Korean Longitudinal Survey of Women & Families International Symposium, 13th of September 2013, Seoul, Korea.

Mishra GD. The 5th Scientific Meeting of the Asian Pacific Menopause Federation, 18th of October 2013, Tokyo, Japan.


1. Vasomotor symptoms and psychological symptoms of depression during menopause : results from a pooled analysis

Chung HF, Pandeya N, Mishra G. Australian Longitudinal Study on Women’s Health Scientific Meeting, 4-5th of May 2016, Newcastle, Australia.

2. Panel presentations: Overview of InterLACE

- Mishra GD. International Collaboration for a Life Course Approach to Women’s Reproductive Health and Chronic Disease Events (InterLACE).

- Anderson D. Obesity and vasomotor symptoms during menopause: results from a pooled analysis.

- Chung HF. Vasomotor symptoms and depressed mood during menopause: results from a pooled analysis.

ICOWHI 21st International Congress on Women's Health, 6-9th of November 2016, Baltimore, USA.